Friday, May 28, 2010

LTP in the Octopus Memory System

I’ll get back to octopus behavior in the subsequent posts, but I want to digress into octopus neurobiology for a minute. We know that octopuses can learn, and our buddy J. Z. Young proposed that their memory system is much like ours – as evidence, he showed that the structure of the octopus vertical lobe (a little chunk of brain tissue that sits right at the top of the octopus brain – see P. Z. Myers’ post on the subject for a quick introduction to the brain of octopus) may have a lot in common with the structure of the mammalian hippocampus (which is a place in the human brain that is critical for memory – it’s shown here.)

The specific paper that I’ll review here is “A Learning and Memory Area in the Octopus Brain Manifests a Vertebrate-Like Long-Term Potentiation” by Hochner et al. It was published in 2003 (7 years ago already!) in the Journal of Neurophysiology (available at this link.) Much as the title suggests, this study showed the presence of long-term potentiation (or LTP) in the octopus vertical lobe.
Let me explain what LTP is, and then the previous paragraph may become a lot more meaningful to some readers. LTP is the mechanism by which synapses (the points of communication between nerve cells) become “stronger”; that is, synapses can transmit information with a varying degree of degradation of the signal, and stronger ones will transmit the information better than weaker ones. First, a picture of a synapse:

The neuron sending the information (the presynaptic neuron) is in yellow, while the neuron receiving the signal (the postsynaptic neuron) is in green. Imagine that the system works like this: an electrical pulse comes flying down the presynaptic axon from the top of the page. When it gets to the end of the axon, it causes (through a variety of rather complicated biochemical mediators) all those synaptic vesicles to dump their contents into the space between the neurons (the synaptic cleft). Their contents are neurotransmitters, which then act on receptors on the postsynaptic neuron. This activity causes electrical currents to be generated in the postsynaptic neuron, and so the electrical signal has bridged the gap and is on its way.
When a synapse is persistently active, it will tend to become stronger (this is known as Hebb’s law – it’s actually only sometimes true, but it’s a good heuristic for now.) This is called long-term potentiation, as the synapse can be said to be potentiated, and this effect will last a while. Now, a lot of things happen during LTP – the synapse may become physically larger or more efficient, and the types of receptors on each side may change. In any case, the overall effect is that the synapse will become better at propagating signals – that is, the same signal in the presynaptic neuron will elicit a larger signal in the postsynaptic neuron.

In this study, electrical pulses were sent through the MSF (medial superior frontal) tract – a tract that runs parallel to the brain surface and interacts with vertical lobe neurons. Simultaneously, recordings were made from neurons in the vertical lobe that could receive signals from the MSF tract. What the experimenters were testing was whether they could induce LTP in octopus neurons by stimulating them. This procedure is known to work in vertebrates, and is thought to be responsible for much of vertebrate neural plasticity (that is, the adjustment of the way neurons are “wired” together, which is thought to allow us to do things like learn and remember.) If it’s present in octopus, then it means that there is something about the organization of this type of system that is efficient or effective enough to have evolved largely independently in two very different groups of animals (although we don’t actually know exactly what the last common evolutionary ancestor was between people and octopus, we have a pretty good idea – but that’s for another post. It suffices to say that it mostly likely had a very simple nervous system, meaning that octopus and vertebrate brains evolved mostly independently.)

If you’ve read my previous post or another piece of writing about the squid giant axon, let me use this example to drive home its significance. The techniques of neural stimulation and recording in this paper, as well as the theories that the authors employ about the structure and function of neurons, all descend directly from work done on the squid giant axon. It really is a big deal.

So, with the basic experimental design and that little editorial out of the way, let’s hit the meat of the paper:

All of this groups work was done in vertical lobe slices; that is, they anesthetized the octopus by submerging it in a weak ethanol solution, removed a slice of its brain, and kept the brain slice alive in a solution of artificial seawater and antibiotics for a day before experimenting on it.

This figure shows the anatomy of the vertical lobe/MSF tract system. To make it clear, if you imagine an octopus sitting on the ground, the octopus’s tentacles and mouth would be to the right of this figure, and its mantle would be to the left.

This figure shows the location of recording and stimulation electrodes. The graphs are tracings of the voltage recorded by the recording electrode. The authors identify two signals – the large one (TP) is from neurons in the MSF tract, and the small one after it (shown in this figure by arrow heads) is from the vertical lobe neurons that the MSF tract makes synapses with. They are delayed in time simply because it takes some time for a signal to travel down a neuron. In this case, the authors measured the size of each signal, measured as the maximum height of the tracing.

This is a summary of the results of this experiment. After repeated stimulation, most of their test preparations showed a large significant increase in the strength of the synapse, meaning that the same presynaptic signal generated a larger postsynaptic signal. This is a sort of weird graph, so let me explain it: the horizontal axis shows the significant of the trial - the ones to the left are significant, whereas that group on the right is not significant (meaning they didn't actually show any change.) The vertical axis shows how strong the synapse was after LTP-inducing stimulation, proportional to how strong it was before - that is, "2" means that the synapse is twice as strong after stimulation as it was before, "3" means it is 3 times as strong, etc.

In this figure, the top graph represents the size of the recorded signals in postsynaptic neurons of the vertical lobe (that is, field-type postsynaptic potentials, or fPSP.) The bottom graph represents recordings from the presynaptic MSF neurons. The arrows show the beginning and the end of LTP-inducing stimulation. This figure is very informative, as it shows us that the synapse is indeed selective strengthened. The presynaptic signal (TP – bottom graph) does not increase, but the postsynaptic potential (fPSP – top graph) becomes at least twice as strong as it was prior to stimulation. To sum it up, the presynaptic signal stays the same, but because the synapses have become better at transmitting the signal, the postsynaptic signal is larger.

This is good evidence that LTP takes place in the memory system of the octopus brain, and could account for the memory of octopuses, as we suspect it accounts for much of the memory ability of humans. The rest of the paper is spent elucidating possible mechanisms which could account for the observed LTP, as well as verifying that it is actually LTP and not just an artifact of their procedure – I don’t have the time to go through this at the moment, mostly because it involves a wide array of neurophysiological techniques, which are a workout to explain in and of themselves. (For the curious neurophysiologically-minded readers, I'll summarize: they find that there are both postsynaptic and presynaptic mechanisms that contribute to LTP in octopuses, as in vertebrates. It is also demonstrated that LTP in the octopus involves a large increase in intracellular calcium concentration, as in vertebrates. Unlike in most vertebrate systems, however, LTP in octopuses is not NMDA-type receptor dependent, although the authors don't offer an alternative explanation. This is neat, because it suggests that the same sorts of neural systems are likely to evolve with some wiggle room as to the specific mechanisms of their functioning.)

Why does this study matter? It implies that this specific type of organization and functioning of a memory system is somehow “special” – that is, it works so much better than an alternative arrangement that it was selected for in (at least) two independent cases. In terms of studying octopus biology, it also means that the great wealth of information on vertebrate neural systems is likely to be applicable (at least in a modified form) to the study of cephalopod nervous systems. In terms of studying vertebrate biology, it is possible that studying how this system work in octopus could give us new insights into the function of vertebrate memory systems. Lastly, the methods used in this paper are just incredibly cool. C’mon, people – keeping octopus brains alive in a bath! Imagine how awesome it would be to explain your job to somebody at a dinner party if you were the experimenter.

If you read this and find yourself with any questions, or noticing any errors, please let me know. I know this was a bit technical, but I think it’s misleading to present science as if it were possible to really grasp it without being at least a bit technical. I think to really understand the importance of research like this, you have to understand the procedures used, at least basically. In any case, I hope this post was informative and interesting.